CAJ | 학술논문

目的：探讨甲泼尼龙对高血压脑出血大鼠脑组织水通道蛋白4(aquaporin-4, AQP-4)和S100蛋白的影响。方法64只大鼠随机分为假手术组(8只)、生理盐水对照组(8只)和甲泼尼龙组(48只),甲泼尼龙组再根据模型制作至甲泼尼龙干预的时间间隔分为2、4、8、12、24、48 h亚组,每亚组8只。甲泼尼龙组在相应时间点腹腔注射甲泼尼龙(首次30 mg/kg,然后15 mg/kg,1次/6 h,共3 d),生理盐水对照组腹腔注射等体积生理盐水。甲泼尼龙干预后24 h和72 h进行神经行为学评分。应用干湿重法检测大脑半球含水量,原位杂交和免疫组化染色法分别检测AQP-4 mRNA和蛋白表达。应用免疫组织化学双标法检测AQP-4和S100蛋白表达。结果与假手术组比较,生理盐水对照组AQP-4表达水平和脑组织含水量显著增高(P均<0．05)。与生理盐水对照组比较,早期给予甲泼尼龙组(2 h、4 h和8 h亚组)神经功能评分、AQP-4 mRNA和蛋白表达水平以及脑含水量均显著降低(P均<0．05)。免疫组织化学双重染色显示,早期给予甲泼尼龙组(2 h、4 h和8 h亚组)AQP-4蛋白和S100蛋白表达也较生理盐水对照组显著降低( P均<0．05)。结论早期应用甲泼尼龙能下调高血压脑出血大鼠脑组织AQP-4和S100蛋白表达,从而减轻脑出血后脑水肿。
목적：탐토갑발니룡대고혈압뇌출혈대서뇌조직수통도단백4(aquaporin-4, AQP-4)화S100단백적영향。방법64지대서수궤분위가수술조(8지)、생리염수대조조(8지)화갑발니룡조(48지),갑발니룡조재근거모형제작지갑발니룡간예적시간간격분위2、4、8、12、24、48 h아조,매아조8지。갑발니룡조재상응시간점복강주사갑발니룡(수차30 mg/kg,연후15 mg/kg,1차/6 h,공3 d),생리염수대조조복강주사등체적생리염수。갑발니룡간예후24 h화72 h진행신경행위학평분。응용간습중법검측대뇌반구함수량,원위잡교화면역조화염색법분별검측AQP-4 mRNA화단백표체。응용면역조직화학쌍표법검측AQP-4화S100단백표체。결과여가수술조비교,생리염수대조조AQP-4표체수평화뇌조직함수량현저증고(P균<0．05)。여생리염수대조조비교,조기급여갑발니룡조(2 h、4 h화8 h아조)신경공능평분、AQP-4 mRNA화단백표체수평이급뇌함수량균현저강저(P균<0．05)。면역조직화학쌍중염색현시,조기급여갑발니룡조(2 h、4 h화8 h아조)AQP-4단백화S100단백표체야교생리염수대조조현저강저( P균<0．05)。결론조기응용갑발니룡능하조고혈압뇌출혈대서뇌조직AQP-4화S100단백표체,종이감경뇌출혈후뇌수종。
Objective To observe the effect of methylprednisolone on the expression levels of aquaporin-4 (AQP-4) and S100 protein in brain tissue of hypertensive intracerebral hemorrhage in rats and to investigate the treatment timing and the possible neuroprotective mechanism of methylprednisolone for hypertensive intracerebral hemorrhage. Methods Sixty-four rats were randomly divided into 3 groups:a sham operation group ( n= 8 ), a control group ( n= 8 ), and a methylprednisolone group ( n= 48 ). The methylprednisolone group was redivided into 2, 4, 8, 12, 24, and 48 hsubgroups (n=8 in each subgroup) according to the modeling to the time intervals of methylprednisolone treatment. Methylprednisolone was administered intraperitoneal y (30 mg/kg fol owed by 15 mg/kg every 6 hours for 3 d) at the corresponding time points in the methylprednisolone group, and the equal volume normal saline was administered intraperitoneal y in the control group. Neurological behavior score was conducted at 24 and 72 h after methylprednisolone treatment. The dry-wet weight method was used to measure hemispheric water content. In situ hybridization and immunohistochemical staining were used to detect the expression changes of AQP-4 mRNA and AQP-4 protein respectively. Double staining immunohistochemistry was used to detect AQP-4 and S100 protein. Results Compared with the sham operation group, the expression level of AQP-4 and brain water content in the control group were significantly increased (al P<0. 05). Compared with the control group, the neurological scores, expression levels of AQP-4 mRNA and protein, as wel as the brain water content in early methylprednisolone subgroups (2 h, 4 h and 8 hsubgroups) were significantly decreased (al P<0. 05). Double staining immunohistochemistry showed that expression levels of AQP-4 and S100 protein in early methylprednisolone subgroups (2 h, 4 h and 8 hsubgroups) were significantly decreased than those in the control group (al P<0. 05). Conclusions Early methylprednisolone may downregulate the expression levels of AQP-4 and S100 protein in the brain tissue after hypertensive intracerebral hemorrhage in rats, and thus attenuate brain edema after intracerebral hemorrhage.